Efflux pump inhibitors: new updates

AlMatar, Manaf; Albarri, Osman; Makky, Essam A.; Köksal, Fatih

doi:10.1007/s43440-020-00160-9

Cited by 59 publications

(62 citation statements)

References 116 publications

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“…Ivermectin is a potential drug against COVID-19 infection yet to be approved and recommended only for clinical trial [ 18 , 19 , 38 ]. In our study, we observed using this anti-parasitic drug for COVID-19 treatment.…”

Section: Discussionmentioning

confidence: 99%

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Use of Antimicrobials among Suspected COVID-19 Patients at Selected Hospitals, Bangladesh: Findings from the First Wave of COVID-19 Pandemic

et al. 2021

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Antimicrobials are empirically used in COVID-19 patients resulting in increased antimicrobial resistance. Our objective was to assess antimicrobial use among suspected COVID-19 in-patients. From March to August 2020, we collected data from in-patients of 12 tertiary-level hospitals across Bangladesh. We identified suspected COVID-19 patients; collected information on antimicrobial received within 24 h before and on hospitalization; tested nasopharyngeal swab for SARS-CoV-2 using rRT-PCR. We used descriptive statistics and a regression model for data analysis. Among 1188 suspected COVID-19 patients, 69% were male, 40% had comorbidities, and 53% required oxygen. Antibiotics were used in 92% of patients, 47% within 24 h before, and 89% on admission. Patients also received antiviral (1%) and antiparasitic drugs (3%). Third-generation cephalosporin use was the highest (708; 60%), followed by macrolide (481; 40%), and the majority (853; 78%) who took antibiotics were SARS-CoV-2 negative. On admission, 77% mild and 94% moderately ill patients received antibiotics. Antibiotic use on admission was higher among severely ill patients (AOR = 11.7; 95% CI: 4.5–30.1) and those who received antibiotics within 24 h before hospital admission (AOR = 1.6; 95% CI: 1.0–2.5). Antimicrobial use was highly prevalent among suspected COVID-19 in-patients in Bangladesh. Initiating treatment with third-generation cephalosporin among mild to moderately ill patients was common. Promoting antimicrobial stewardship with monitoring is essential to prevent blanket antibiotic use, thereby mitigating antimicrobial resistance.

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Section: Discussionmentioning

confidence: 99%

“…In our study, we observed using this anti-parasitic drug for COVID-19 treatment. One possible reason for using could be the antiviral property of this drug [ 38 ]. However, clinicians should hold back its use until it is fully recommended for the treatment of COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Use of Antimicrobials among Suspected COVID-19 Patients at Selected Hospitals, Bangladesh: Findings from the First Wave of COVID-19 Pandemic

et al. 2021

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“…This comparison shows that the drug-binding sites and RNA-binding sites share only one residue (F66) and that the above compounds mainly bind to the different sites from those for RNA-binding. Ivermectin, an anti-parasitic drug with antiviral properties, has also been shown to bind to the similar region as the above compounds [ 32 ]. Although each compound also interacts with the residues of the NTD other than those shown in Figure 3 a, none of these residues overlaps with the RNA-binding region except for rapamycin, which shares K65 with the RNA-binding sites [ 31 ].…”

Section: Molecular Flexibility and Drug Binding Of N Cov2mentioning

confidence: 99%

Viewing SARS-CoV-2 Nucleocapsid Protein in Terms of Molecular Flexibility

Matsuo

2021

Biology

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The latest coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19) pneumonia leading to the pandemic, contains 29 proteins. Among them, nucleocapsid protein (NCoV2) is one of the abundant proteins and shows multiple functions including packaging the RNA genome during the infection cycle. It has also emerged as a potential drug target. In this review, the current status of the research of NCoV2 is described in terms of molecular structure and dynamics. NCoV2 consists of two domains, i.e., the N-terminal domain (NTD) and the C-terminal domain (CTD) with a disordered region between them. Recent simulation studies have identified several potential drugs that can bind to NTD or CTD with high affinity. Moreover, it was shown that the degree of flexibility in the disordered region has a large effect on drug binding rate, suggesting the importance of molecular flexibility for the NCoV2 function. Molecular flexibility has also been shown to be integral to the formation of droplets, where NCoV2, RNA and/or other viral proteins gather through liquid-liquid phase separation and considered important for viral replication. Finally, as one of the future research directions, a strategy for obtaining the structural and dynamical information on the proteins contained in droplets is presented.

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“…The current evidence from some separate retrospective studies in Covid-19 patients has shown that a baseline statin treatment was associated with a lower severity of disease [ [136] , [137] , [138] ] and a reduced mortality [ [139] , [140] , [141] , [142] , [143] , [144] , [145] , [146] ], although two studies did not find any association between exposure to statins and the outcome of Covid-19 infection [ 147 , 148 ]. Furthermore, some meta-analyses have been recently performed, globally revealing an overall 27–50% reduction, with respect to the control patients, in the pooled risk of developing severe form/mortality from Covid-19 [ [149] , [150] , [151] , [152] ], with the evidence of a marked patient heterogeneity in the various observations [ 151 , 152 ], in particular considering the qualitative difference between pre-admission and in-hospital use of statins [ 150 , 153 ]. Although precious and fortunate, these correlation data are very global, gathering various statin molecules and administered doses (more or less efficient on the treated hypercholesterolemia).…”

Section: Proposed Anti-covid19 Repurposing For Statinsmentioning

confidence: 99%

Coronaviruses, cholesterol and statins: Involvement and application for Covid-19

2021

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The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo , besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.

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Efflux pump inhibitors: new updates

Cited by 59 publications

References 116 publications

Use of Antimicrobials among Suspected COVID-19 Patients at Selected Hospitals, Bangladesh: Findings from the First Wave of COVID-19 Pandemic

Use of Antimicrobials among Suspected COVID-19 Patients at Selected Hospitals, Bangladesh: Findings from the First Wave of COVID-19 Pandemic

Viewing SARS-CoV-2 Nucleocapsid Protein in Terms of Molecular Flexibility

Coronaviruses, cholesterol and statins: Involvement and application for Covid-19

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